MYO1B enhances colorectal cancer metastasis by promoting the F-actin rearrangement and focal adhesion assembly via RhoA/ROCK/FAK signaling.

MYO1B enhances colorectal cancer metastasis by promoting the F-actin rearrangement and focal adhesion assembly via RhoA/ROCK/FAK signaling.
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DOI:
10.21037/atm-21-4702
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发表时间:
2021-10
影响因子:
--
通讯作者:
Cui C
Cui C
中科院分区:
医学4区
文献类型:
--
作者:
Xie L;Huang H;Zheng Z;Yang Q;Wang S;Chen Y;Yu J;Cui C

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结直肠癌(CRC)在全球范围内具有很高的发病率和死亡率。肿瘤转移是结直肠癌患者预后不良的主要原因之一。然而,CRC转移的机制仍不清楚。肌球蛋白 1B (MYO1B) 对于细胞迁移和运动很重要,是包含各种肌球蛋白的肌球蛋白超家族的一部分。对前列腺癌、宫颈癌和头颈癌的研究揭示了有关 MYO1B 对肿瘤转移影响的初步发现。然而,MYO1B 在 CRC 转移中的作用及其潜在机制仍不清楚。采用实时定量PCR和免疫组化染色方法分析MYO1B在人结直肠癌和正常粘膜组织中的表达。基于慢病毒载体的 MYO1B 寡核苷酸和短发夹 RNA (shRNA) 用于检查 MYO1B 在 CRC 细胞中的功能相关性。使用免疫共沉淀、蛋白质印迹和免疫荧光测定来研究 MYO1B 介导的细胞迁移的潜在机制。 MYO1B在大多数结直肠癌组织中表达增加,并与肿瘤转移风险增大和患者预后不良呈正相关。 MYO1B 与 CRC 细胞的体外和体内迁移和侵袭特性显着相关。 MYO1B 通过增强 RhoA 的激活,通过 ROCK2/LIMK/Cofilin 轴促进 F-肌动蛋白重排。 MYO1B 还通过靶向 RhoA 促进粘着斑的组装。 MYO1B 通过促进 RhoA 的激活在 CRC 转移中发挥重要作用。 MYO1B不仅可能是预测CRC转移风险和不良预后的有效生物标志物,而且还可能成为肿瘤转移高风险患者的潜在治疗靶点。
Colorectal cancer (CRC) has a high worldwide incidence and mortality. Tumor metastasis is one of the primary reasons for the poor prognosis of CRC patients. However, the mechanism underlying CRC metastasis is still unclear. Myosin 1B (MYO1B) is important for cell migration and motility and is part of the myosin superfamily that contains various myosins. Studies of prostate, cervical, and head and neck cancer have revealed preliminary findings concerning the effect of MYO1B on tumor metastasis. However, the role of MYO1B in CRC metastasis, as well as its underlying mechanism, remains unknown. Quantitative real-time PCR and immunohistochemical staining methods were used to analyze the expression of MYO1B in human CRC and normal mucosa tissues. Lentivirus vector-based MYO1B oligonucleotides and short hairpin RNA (shRNA) were used to examine the functional relevance of MYO1B in CRC cells. Co-immunoprecipitation, western blotting, and immunofluorescence assays were used to investigate the underlying mechanism of MYO1B-mediated cell migration. The expression of MYO1B was increased in most CRC tissues and was positively associated with a greater risk of tumor metastasis and poor prognosis for patients. MYO1B was significantly associated with the migration and invasion properties of CRC cells in vitro and in vivo. MYO1B promoted F-actin rearrangement through the ROCK2/LIMK/Cofilin axis by enhancing the activation of RhoA. MYO1B also promoted the assembly of focal adhesions by targeting RhoA. MYO1B plays a vital role in CRC metastasis by promoting the activation of RhoA. MYO1B may not only be a valid biomarker for predicting the risk of metastasis and poor prognosis in CRC but may also be a potential therapeutic target for patients with a high risk of tumor metastasis.
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